In recent years, autogenic or allogenic transplantation of cultured mesenchymal stem cells, osteoblasts, chondrocytes, periodontal cells, dental pulp cells and the like has been reported to be effective for repairing loss of cartilage, bone and/or periodontium or dental pulp caused by disorders of cartilage, bone or dental conditions such as bone fracture, osteoarthritis, cartilage injury, myeloma, periodontal disease, pulpitis and the like. However, transplantation of such cultured cells can lead to damage or destruction of the transplanted cells due to the surrounding tissue or inflammatory or immune cell activation, in many cases resulting in deciduation, absorption or necrosis of the transplanted tissue. Since dental pulp cells, having a minimal extracellular matrix, are particularly susceptible to peeling by mechanical stimuli, it has been difficult to provide cultured dental pulp cells for transplantation.
In order to facilitate fixation of transplanted tissue into surrounding tissue and thus promote repair of the tissue, it is important for the cells of the transplanted tissue to maintain resistance against external stimuli from the surrounding tissue or from inflammatory or immune cell activation, and specifically against mechanical stimuli and/or proteolytic reactions. In addition, increased resistance to external stimulus of immature cells and/or tissues in repairing or regenerating mesenchyme, bone, cartilage, periodontum or dental pulp has been found to be effective for treatment of various bone, cartilage or periodontal or dental pulp diseases.
Transplant tissues have been therefore encapsulated in glass fibers or in immunoisolation membranes. For example, insulin-producing mouse Langerhans cells are usually encapsulated in an immunoisolation membrane for transplant into diabetes patients. However, artificial materials are disadvantageous in that they can provoke immunological rejection and have low adhesion strength. Immunoisolation membranes are problematic because they require laborious synthesis of high-strength polymer films that allow adequate passage of beneficial proteins secreted by cells, as well as enzymes and nutrients, without permitting passage of immune complement proteins (PNE, Vol. 45, No. 13(2000), pp. 2139-2141, 2171-2178, 2307-2312). Although other strategies have included the use of immunosuppressants, extracorporeal circulation of the blood through artificial organs made of cultured cells, and transplantation to locations with low immune cell-induced rejection while avoiding the deficient or impaired sites which are most prone to immune response, such strategies have drawbacks including side-effects of immunosuppressant, the burden of extracorporeal circulation on patients, and the remaining of deficient or impaired sites. It has therefore been desired to confer resistance to the actual cells and/or tissues.
Lectins are ligand-specific sugar-binding proteins with bivalent or more valence found mainly in plants and animals, having activities of agglutinating various types of animal and plant cells and precipitating polysaccharides or complex carbohydrates. Some lectins, such as concanavalin A, are known to exhibit activity for promoting juvenilization of T cells. The effects of different lectins on differentiation and proliferation of chondrocytes have been studied, and it has been reported that lectins (such as concanavalin A) with affinity for α-D-mannose residues and α-D-glucose residues powerfully promote differentiation of chondrocytes, based on increased proteoglycan synthesis (Yan et al., J. Biol. Chem., Vol. 265, pp. 10125-10131, 1990). Nevertheless, it has not been known whether concanavalin A and other lectins can confer resistance against external stimulus to animal cells, particularly cultured cells, and/or various types of tissue in the living bodies.